P1390: THE EFFICACY AND SAFETY OF MODIFIED MELPHALAN AND BUSULFAN-BASED REGIMEN FOR ALLOGENEIC TRANSPLANTATION IN REFRACTORY/RELAPSED AML PATIENTS
Authors: S. Chen, X. Zhang, W. Zhai, Y. He, S. Feng, M. Han, T. Niu, Y. Xu, G. Gao, S. Fan, Z. Zhou, F. Zhou, F. Li, L. Liu, W. Yang, Q. Liu, X. Zhang, E. Jiang
Journal: HemaSphere (2022)

Background: Allogeneic Hematopoietic stem cell transplantation (Allo-HSCT) offers the only survival opportunity for refractory/relapsed (R/R) AML patients, as those patients responded insufficiently to chemotherapy. However, the overall survival (OS) rate after HSCT is reported to be only 20~40%. Aims: In this study, we made refinements in the conditioning regimen with both melphalan and busulfan, namely MCBC (the combination of melphalan, cladribine, busulfan, and cyclophosphamide). We aim to investigate the efficacy and safety of MCBC conditioning regimen for allo-HSCT in R/R AML patients. Methods: This prospective multi-center clinical trial was conducted in 12 tertiary hospitals in China, and enrolled R/R AML patients underwent allo-HSCT from March 2020 to January 2022(ChiCTR Registration ID: ChiCTR2000029936). The protocol was approved by institutional review boards at participating centers. All patients enrolled received MCBC preconditioning regimen: melphalan 60mg/m2/d, day -9~-8, cladribine 5mg/m2/d, day -7~-5, busulfan 3.2mg/kg/d, day -5~-3, cyclophosphamide 30mg/kg/d, day -2~-1. Rabbit ATG was added in haploid-identical and unrelated-matched donor transplantation. FK506/CsA +short course MTX±MMF was mostly used to prevent graft-versus-host disease（GVHD）. A post-transplantation consolidation treatment was provided whenever possible, including low-dose azacytidine, venetoclax, or FLT3 inhibitors. Probabilities of OS, DFS were calculated by Kaplan-Meier method. COX regression model was used for multivariate analysis. Results: This study included 56 R/R AML patients, including 48 refractory and 8 relapsed AML. Only 7 patients achieved hematology remission before transplantation, and the blast count, measure by flow MRD pre-HSCT, of 25 patients was ≥ 20%. It is inspiring that hematopoietic reconstitution was achieved in all 56 patients, and all patients (100%) achieved hematology complete remission (CR) on day +14. With a median follow-up of 186（48-555）days, the estimated 1-year overall survival (OS) and 1-year disease-free survival (DFS) were 77.8±7.72% and 71.9±7.46%, respectively. 11 patients relapsed within the 1st year, and the median time from HSCT to relapse was 105 (83-184) days. The probability of relapsed rate was 32.4±8.3%, and non-relapse mortality (NRM) was 3.7±2.6%. Infection is the leading NRM cause. The incidence of Ⅲ and Ⅳ aGVHD was 10.71%. We furtherly performed univariant and multivariant analyses to identify the independent predictors of poor outcomes. Univariate analysis results revealed blast count ≥ 20% before transplantation, and absence of maintenance treatment post-HSCT were the risk factors that affected prognosis. Competitive risk modal analysis for multivariate analysis showed both high blast count pre-HSCT (HR 1.496, p=0.0015) and absence of maintenance treatment after HSCT (HR 2.050, p=0.0170) was the independent factor. Mucositis was the main reported regimen-related toxicity, and it was well tolerated. Image:Summary/Conclusion: Our study confirms the excellent anti-leukemic capacity and good acceptable toxicity of MCBC conditioning regimen in R/R AML, that more than 70% patients could achieve leukemia free survival within the 1st year after allo-HSCT. Furthermore, it is important to decrease leukemic blast burden pre-HSCT and perform maintenance treatment after transplantation as soon as possible.